TY - JOUR
T1 - Apoptosis-inducing factor (AIF)
T2 - A ubiquitous mitochondrial oxidoreductase involved in apoptosis
AU - Daugas, Eric
AU - Nochy, Dominique
AU - Ravagnan, Luigi
AU - Loeffler, Markus
AU - Susin, Santos A.
AU - Zamzami, Naoufal
AU - Kroemer, Guido
N1 - Funding Information:
We thank Christiane Martingou and Geneviève Piétu (CNRS-ERS1984, Villejuif, France) for Northern blot analysis, See-DNA Biotech Inc. (Toronto, Canada) for mouse FISH, and Nicole Pfister for histology. This work has been supported by a special grant form the Ligue Nationale contre le Cancer, as well as by grants from ANRS, FRM, EU (to G.K.), Assistance Publique-Hôpitaux de Paris and CANAM (Contract 98006 to E.D.).
PY - 2000/7/7
Y1 - 2000/7/7
N2 - Apoptosis-inducing factor (AIF) is encoded by one single gene located on the X chromosome. AIF is ubiquitously expressed, both in normal tissues and in a variety of cancer cell lines. The AIF precursor is synthesized in the cytosol and is imported into mitochondria. The mature AIF protein, a flavoprotein (prosthetic group: flavine adenine dinucleotide) with significant homology to plant ascorbate reductases and bacterial NADH oxidases, is normally confined to the mitochondrial intermembrane space. In a variety of different apoptosis-inducing conditions, AIF translocates through the outer mitochondrial membrane to the cytosol and to the nucleus. Ectopic (extra-mitochondrial) AIF induces nuclear chromatin condensation, as well as large scale (~50 kb) DNA fragmentation. Thus, similar to cytochrome c, AIF is a phylogenetically old, bifunctional protein with an electron acceptor/donor (oxidoreductase) function and a second apoptogenic function. In contrast to cytochrome c, however, AIF acts in a caspase-independent fashion. The molecular mechanisms via which AIF induces apoptosis are discussed. Copyright (C) 2000 Federation of European Biochemical Societies.
AB - Apoptosis-inducing factor (AIF) is encoded by one single gene located on the X chromosome. AIF is ubiquitously expressed, both in normal tissues and in a variety of cancer cell lines. The AIF precursor is synthesized in the cytosol and is imported into mitochondria. The mature AIF protein, a flavoprotein (prosthetic group: flavine adenine dinucleotide) with significant homology to plant ascorbate reductases and bacterial NADH oxidases, is normally confined to the mitochondrial intermembrane space. In a variety of different apoptosis-inducing conditions, AIF translocates through the outer mitochondrial membrane to the cytosol and to the nucleus. Ectopic (extra-mitochondrial) AIF induces nuclear chromatin condensation, as well as large scale (~50 kb) DNA fragmentation. Thus, similar to cytochrome c, AIF is a phylogenetically old, bifunctional protein with an electron acceptor/donor (oxidoreductase) function and a second apoptogenic function. In contrast to cytochrome c, however, AIF acts in a caspase-independent fashion. The molecular mechanisms via which AIF induces apoptosis are discussed. Copyright (C) 2000 Federation of European Biochemical Societies.
KW - Apoptosis-inducing factor
KW - Bcl-2
KW - Cytochrome c
KW - Mitochondrion
KW - Programmed cell death
UR - http://www.scopus.com/inward/record.url?scp=0034617449&partnerID=8YFLogxK
U2 - 10.1016/S0014-5793(00)01731-2
DO - 10.1016/S0014-5793(00)01731-2
M3 - Short survey
C2 - 10913597
AN - SCOPUS:0034617449
SN - 0014-5793
VL - 476
SP - 118
EP - 123
JO - FEBS Letters
JF - FEBS Letters
IS - 3
ER -